Binding mode of conformations and structure-based pharmacophore development for farnesyltransferase inhibitors

Farnesyltransferase (FTase) is one of the prenyltransferase family enzymes that catalyse the transfer of 15-membered isoprenoid (farnesyl) moiety to the cysteine of CAAX motif-containing proteins including Rho and Ras family of G proteins. Inhibitors of FTase act as drugs for cancer, malaria, progeria and other diseases. In the present investigation, we have developed two structure-based pharmacophore models from protein–ligand complex (3E33 and 3E37) obtained from the protein data bank. Molecular dynamics (MD) simulations were performed on the complexes, and different conformers of the same complex were generated. These conformers were undergone protein–ligand interaction fingerprint (PLIF) analysis, and the fingerprint bits have been used for structure-based pharmacophore model development. The PLIF results showed that Lys164, Tyr166, TrpB106 and TyrB361 are the major interacting residues in both the complexes. The RMSD and RMSF analyses on the MD-simulated systems showed that the absence of FPP in the complex 3E37 has significant effect in the conformational changes of the ligands. During this conformational change, some interactions between the protein and the ligands are lost, but regained after some simulations (after 2 ns). The structure-based pharmacophore models showed that the hydrophobic and acceptor contours are predominantly present in the models. The pharmacophore models were validated using reference compounds, which significantly identified as HITs with smaller RMSD values. The developed structure-based pharmacophore models are significant, and the methodology used in this study is novel from the existing methods (the original X-ray crystallographic coordination of the ligands is used for the model building). In our study, along with the original coordination of the ligand, different conformers of the same complex (protein–ligand) are used. It concluded that the developed methodology is significant for the virtual screening of novel molecules on different targets.     

Exophytic gliomas of the spinal cord

Intradural extramedullary glial tumours of the spinal cord are rare. We report for such tumours arising from the dorsal cord. Myelography and operative findings were almost similar to that of an intradural neurofibroma. Surgical removal had resulted in rewarding neurological recovery. One of them had a recurrence after six years and was re-explored. Anterolateral attachment near the root entry zone suggests its origin probably from the spinal cord with an exophytic growth.     

A framework for evaluating image segmentation algorithms.

The purpose of this paper is to describe a framework for evaluating image segmentation algorithms. Image segmentation consists of object recognition and delineation. For evaluating segmentation methods, three factors-precision (reliability), accuracy (validity), and efficiency (viability)-need to be considered for both recognition and delineation. To assess precision, we need to choose a figure of merit, repeat segmentation considering all sources of variation, and determine variations in figure of merit via statistical analysis. It is impossible usually to establish true segmentation. Hence, to assess accuracy, we need to choose a surrogate of true segmentation and proceed as for precision. In determining accuracy, it may be important to consider different 'landmark' areas of the structure to be segmented depending on the application. To assess efficiency, both the computational and the user time required for algorithm training and for algorithm execution should be measured and analyzed. Precision, accuracy, and efficiency factors have an influence on one another. It is difficult to improve one factor without affecting others. Segmentation methods must be compared based on all three factors, as illustrated in an example wherein two methods are compared in a particular application domain. The weight given to each factor depends on application.     

1.5 tesla magnetic resonance imaging of acute spinal trauma

Fifty patients with spinal injury above L2 were studied with MRI; forty-two had initial and followup studies permitting correlation of MRI abnormalities with neurologic improvement. Two discrete patterns of MRI abnormality were identified, presumably representing cord hemorrhage and edema respectively. A third pattern appeared to represent a mixed type of injury. The correlation between the MRI patterns of cord injury and neurologic recovery was excellent. The ability of MRI to demonstrate and characterize acute cord injury appears to exceed that of other diagnostic techniques.     

Aid for impacted foreign body ear

Foreign body ear is a common problem. When it is impacted it can tax the resorces of each of us. An attempt is made in this paper to make a customable foreign body removal hook using a lumbar puncture needle.     

Holliday junctions in FLP recombination: resolution by step-arrest mutants of FLP protein.

The FLP "recombinase" of the 2-micron circle yeast plasmid can resolve synthetic FLP site-Holliday junctions. Mutants of the FLP protein that are blocked in recombination but are normal in substrate cleavage can also mediate resolution. The products of resolution by these mutants are almost exclusively nicked molecules with a protein-bound 3' end. There is no significant asymmetry in strand cleavage (top versus bottom) by the mutants in linear or in circular FLP substrates; nor is there a bias in resolution (toward parentals or toward recombinants) of Holliday junctions (corresponding to top- or to bottom-strand exchange) by wild-type FLP. During normal FLP recombination, a small amount of the expected Holliday intermediate can be detected.     

The value of fine-needle aspiration biopsy in the cytodiagnosis of salivary gland lesions

Fine-needle aspiration cytology (FNAC) was performed on 195 cases of salivary gland lesions. The smears were technically adequate in 178 cases. Tissue examination was available for subsequent histocytologic correlation in 57 cases. The cytodiagnosis included inflammatory lesions (59) and benign (68) and malignant (51) tumors (total, 119). The accuracy of cytodiagnosis was 87.7% with a sensitivity of 80.9% and a specificity of 94.3%. Exact histologic typing was possible in 61.9% of the malignant tumors. Mucoepidermoid tumors and cellular-atypical pleomorphic adenoma posed difficulties in cytodiagnosis.